Clinically Approved Drugs Inhibit the Staphylococcus aureus Multidrug NorA Efflux Pump and Reduce Biofilm Formation

Staphylococcus aureus has acquired resistance to antibiotics since their first use. The S. aureus protein NorA, an efflux pump belonging to the major facilitator superfamily (MFS), contributes to resistance to fluoroquinolones (e.g., ciprofloxacin), biocides, dyes, quaternary ammonium compounds, and antiseptics. Different compounds have been identified as potential efflux pump inhibitors (EPIs) of NorA that result in increased intracellular concentration of antibiotics, restoring their antibacterial activity and cell susceptibility. However, none of the currently known EPIs have been approved for clinical use, probably due to their toxicity profiles. In the present study, we screened approved drugs for possible efflux pump inhibition. By screening a compound library of approximately 1200 different drugs, we identified nilotinib, a tyrosine kinase inhibitor, as showing the best efflux pump inhibitory activity, with a fractional inhibitory concentration index of 0.1875, indicating synergism with ciprofloxacin, and a minimum effective concentration as low as 0.195 μM. Moreover, at 0.39 μM, nilotinib, in combination with 8 μg/mL of ciprofloxacin, led to a significant reduction in biofilm formation and preformed mature biofilms. This is the first description of an approved drug that can be used as an efflux pump inhibitor and to reduce biofilms formation at clinically achievable concentrations

Annual variability of ice-nucleating particle concentrations at different Arctic locations

Abstract. Number concentrations of ice-nucleating particles (NINP) in the Arctic were derived from ground-based filter samples. Examined samples had been collected in Alert (Nunavut, northern Canadian archipelago on Ellesmere Island), Utqiaġvik, formerly known as Barrow (Alaska), Ny-Ålesund (Svalbard), and at the Villum Research Station (VRS; northern Greenland). For the former two stations, examined filters span a full yearly cycle. For VRS, 10 weekly samples, mostly from different months of one year, were included. Samples from Ny-Ålesund were collected during the months from March until September of one year. At all four stations, highest concentrations were found in the summer months from roughly June to September. For those stations with sufficient data coverage, an annual cycle can be seen. The spectra of NINP observed at the highest temperatures, i.e., those obtained for summer months, showed the presence of INPs that nucleate ice up to −5 ∘C. Although the nature of these highly ice-active INPs could not be determined in this study, it often has been described in the literature that ice activity observed at such high temperatures originates from the presence of ice-active material of biogenic origin. Spectra observed at the lowest temperatures, i.e., those derived for winter months, were on the lower end of the respective values from the literature on Arctic INPs or INPs from midlatitude continental sites, to which a comparison is presented herein. An analysis concerning the origin of INPs that were ice active at high temperatures was carried out using back trajectories and satellite information. Both terrestrial locations in the Arctic and the adjacent sea were found to be possible source areas for highly active INPs

Ship-based measurements of ice nuclei concentrations over the Arctic, Atlantic, Pacific and Southern oceans

Ambient concentrations of ice-forming particles measured during ship expeditions are collected and summarised with the aim of determining the spatial distribution and variability in ice nuclei in oceanic regions. The presented data from literature and previously unpublished data from over 23 months of ship-based measurements stretch from the Arctic to the Southern Ocean and include a circumnavigation of Antarctica. In comparison to continental observations, ship-based measurements of ambient ice nuclei show 1 to 2 orders of magnitude lower mean concentrations. To quantify the geographical variability in oceanic areas, the concentration range of potential ice nuclei in different climate zones is analysed by meridionally dividing the expedition tracks into tropical, temperate and polar climate zones. We find that concentrations of ice nuclei in these meridional zones follow temperature spectra with similar slopes but vary in absolute concentration. Typically, the frequency with which specific concentrations of ice nuclei are observed at a certain temperature follows a log-normal distribution. A consequence of the log-normal distribution is that the mean concentration is higher than the most frequently measured concentration. Finally, the potential contribution of ship exhaust to the measured ice nuclei concentration on board research vessels is analysed as function of temperature. We find a sharp onset of the influence at approximately 36 C but none at warmer temperatures that could bias ship-based measurements. © Author(s) 2020. This work is distributed under the Creative Commons Attribution 4.0 License

Standardized organic geochemistry data of sediment core PG2133 from Lake Bolshoe Toko (Yakutia, Russia)

This data set is part of a larger data harmonization effort to make lake sediment core data machine readable and comparable. Here we standardized organic carbon data of sediment core PG2133, retrieved in 2013 from Lake Bolshoe Toko (Yakutia, Russia) at 26 m water depth. The glacial lake Bolshoe Toko is in the deciduous forest mountain area. It lies at an elevation of ca. 919 m a.s.l. with a surface area of ca. 83.243 km2 and a maximum lake water depth of estimated 72.5 m. The 3.75 m sediment core was retrieved by a UWITEC piston corer during the RU-Land_2013_Yakutia expedition of the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research (AWI, Germany, Potsdam) in cooperation with the North Eastern Federal State University (NEFU, Russia, Yakutsk). Dried and milled samples were analysed using a Vario EL III carbon-nitrogen-sulphur analyser. Organic carbon content was determined using a Vario MAX C analyser

Standardized grain size data of sediment core PG2133 from Lake Bolshoe Toko (Yakutia, Russia)

This data set is part of a larger data harmonization effort to make lake sediment core data machine readable and comparable. Here we standardized grain-size data of sediment core PG2133, retrieved in 2013 from Lake Bolshoe Toko (Yakutia, Russia) at 26 m water depth. The glacial lake Bolshoe Toko is in the deciduous forest mountain area. It lies at an elevation of ca. 919 m a.s.l. with a surface area of ca. 83.243 km2 and a maximum lake water depth of estimated 72.5 m. The 3.75 m sediment core was retrieved by a UWITEC piston corer during the RU-Land_2013_Yakutia expedition of the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research (AWI, Germany, Potsdam) in cooperation with the North Eastern Federal State University (NEFU, Russia, Yakutsk). Grain-size was measured by laser diffractometry using a Malvern Mastersizer 3000 at AWI Potsdam

Standardized mineral data of sediment core PG2133 from Lake Bolshoe Toko (Yakutia, Russia)

This data set is part of a larger data harmonization effort to make lake sediment core data machine readable and comparable. Here we standardized mineral data of sediment core PG2133, retrieved in 2013 from Lake Bolshoe Toko (Yakutia, Russia) at 26 m water depth. The glacial lake Bolshoe Toko is in the deciduous forest mountain area. It lies at an elevation of ca. 919 m a.s.l. with a surface area of ca. 83.243 km2 and a maximum lake water depth of estimated 72.5 m. The 3.75 m sediment core was retrieved by a UWITEC piston corer during the RU-Land_2013_Yakutia expedition of the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research (AWI, Germany, Potsdam) in cooperation with the North Eastern Federal State University (NEFU, Russia, Yakutsk). Bulk mineralogy was analysed by x-ray diffractometry (XRD) using a (PHILIPS, Netherlands) PW1820 goniometer

Standardized radiocarbon data of sediment core PG2133 from Lake Bolshoe Toko (Yakutia, Russia)

This data set is part of a larger data harmonization effort to make lake sediment core data machine readable and comparable. Here we standardized radiocarbon age data of sediment core PG2133, retrieved in 2013 from Lake Bolshoe Toko (Yakutia, Russia) at 26 m water depth. The glacial lake Bolshoe Toko is in the deciduous forest mountain area. It lies at an elevation of ca. 919 m a.s.l. with a surface area of ca. 83.243 km2 and a maximum lake water depth of estimated 72.5 m. The 3.75 m sediment core was retrieved by a UWITEC piston corer (60mm) during the RU-Land_2013_Yakutia expedition of the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research (AWI, Germany, Potsdam) in cooperation with the North Eastern Federal State University (NEFU, Russia, Yakutsk). Radiocarbon data have been analysed in in the radiocarbon laboratory at Poznan and at AWI Bremerhaven (MICADAS). RES (residuals), SOL (solubles) and TOC (bulk organic carbon)

Standardized element data of sediment core PG2133 from Lake Bolshoe Toko (Yakutia, Russia)

This data set is part of a larger data harmonization effort to make lake sediment core data machine readable and comparable. Here we standardized X-ray fluorescence line scanning (XRF)-based element data of sediment core PG2133, retrieved in 2013 from Lake Bolshoe Toko (Yakutia, Russia) at 26 m water depth. The glacial lake Bolshoe Toko is in the deciduous forest mountain area. It lies at an elevation of ca. 919 m a.s.l. with a surface area of ca. 83.243 km2 and a maximum lake water depth of estimated 72.5 m. The 3.75 m sediment core was retrieved by a UWITEC piston corer during the RU-Land_2013_Yakutia expedition of the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research (AWI, Germany, Potsdam) in cooperation with the North Eastern Federal State University (NEFU, Russia, Yakutsk). The downcore elemental composition was measured using an AVAATECH x-ray fluorescence core scanner at AWI Bremerhaven

Efficacy of high-intensity versus low-intensity psychoanalytically oriented long-term treatments and determinants of outcome: individual participant data Meta-analysis of Long-term Analytic treatment Studies (MeLAS)

Introduction: Long-term psychodynamic/psychoanalytic psychotherapy (LTPP) is a prevalent treatment option for complex mental disorders. Yet, little is known about the role of treatment intensity in LTPP. We present a study protocol for a systematic review and individual participant data (IPD) meta-analysis aggregating and analysing individual data from randomised and quasi-experimental trials by meta-analysis. The purpose is to (1) determine the treatment effectiveness of LTPP with low versus high intensity (up to 2 weekly sessions vs three or more), (2) compare their joint effectiveness to shorter therapies and treatments as usual, (3) identify predictors and moderators of treatment outcomes and (4) determine reciprocal relationships between different outcome domains (symptomatic and structural/personality change) over the courses of LTPP. Methods and analysis: We include studies from (randomised controlled trial, RCT) and quasi-experimental trials, where at least one condition was LTPP of high or low frequency. Long-term treatment is defined as ≥1 year or ≥50 sessions. To be eligible studies must include a standardised outcome measure of symptoms (global or disorder specific) with at least one proof of reliability. The primary outcome is symptom reduction (global or specific), secondary outcome criteria are reliable change, remission, functional capacities, personality, personality functioning and interpersonal pathology. Relevant studies will mainly be identified by searching relevant databases: PubMed, PsycINFO (via EBSCO), Web of Science (via Elsevier), Chochrane’s Central Register of Controlled Trials (via Wiley). Risk of bias will be evaluated in line with the Cochrane assessments tools for quasi-experimental trials and RCTs, respectively. Ethics and dissemination: Aggregation of data from primary trials collected based on ethics votes. Dissemination into clinical practice via open access publications of findings. PROSPERO registration number: CRD42022304982; Pre-results

Ship-based measurements of ice nuclei concentrations over the Arctic, Atlantic, Pacific and Southern oceans

Ambient concentrations of ice-forming particles measured during ship expeditions are collected and summarised with the aim of determining the spatial distribution and variability in ice nuclei in oceanic regions. The presented data from literature and previously unpublished data from over 23 months of ship-based measurements stretch from the Arctic to the Southern Ocean and include a circumnavigation of Antarctica. In comparison to continental observations, ship-based measurements of ambient ice nuclei show 1 to 2 orders of magnitude lower mean concentrations. To quantify the geographical variability in oceanic areas, the concentration range of potential ice nuclei in different climate zones is analysed by meridionally dividing the expedition tracks into tropical, temperate and polar climate zones. We find that concentrations of ice nuclei in these meridional zones follow temperature spectra with similar slopes but vary in absolute concentration. Typically, the frequency with which specific concentrations of ice nuclei are observed at a certain temperature follows a log-normal distribution. A consequence of the log-normal distribution is that the mean concentration is higher than the most frequently measured concentration. Finally, the potential contribution of ship exhaust to the measured ice nuclei concentration on board research vessels is analysed as function of temperature. We find a sharp onset of the influence at approximately −36 ∘C but none at warmer temperatures that could bias ship-based measurements